子痫前期患者胎盘整合素α1与β1及肿瘤坏死因子α的表达及其临床意义

目的:探讨整合素α1、β1与肿瘤坏死因子α在子痫前期患者胎盘组织中的表达及其临床意义。方法:采用免疫组化SP法检测50例子痫前期患者(轻度20例,重度30例)胎盘组织中整合素α1、β1及肿瘤坏死因子α的表达;40例正常孕妇为对照组。结果:子痫前期组胎盘绒毛滋养细胞及蜕膜细胞整合素α1、β1的阳性表达率均明显低于对照组(整合素α1:58.00%和80.00%,P<0.05,整合素β1:56.00%和76.50%,P<0.05);肿瘤坏死因子α的阳性表达率明显高于对照组(肿瘤坏死因子α:80.00%和32.00%,P<0.05)。子痫前期组轻、重度患者整合素α1、β1及肿瘤坏死因子α表达的阳性率分别为整合素α1:75.00%和46.67%,整合素β1:75.00%和43.33%,并随病情程度加重而降低;肿瘤坏死因子α:65.00%和90.00%,并随病情程度加重而升高。整合素α1、β1的表达与胎盘重量及新生儿体重呈正相关。结论:胎盘表达整合素α1、β1与肿瘤坏死因子α异常引起滋养细胞浸润不足,可能是子痫前期的发病因素之一。     

双(α-呋喃甲酸)氧钒的胰岛素样作用

钒作为人体必需的微量元素,在葡萄糖的代谢过程中起着重要作用.大量的体内外研究表明微量元素钒具有"胰岛素样(insulin-mimics)"作用,研究表明它能增加胰岛素的敏感性,是"胰岛素的促进剂(insulin-enhancing agent)",可用于治疗和缓解1型和2型糖尿病.     

栀子苷预处理对家兔急性胰腺炎TNF-α、IL-6的影响

目的观察栀子苷预处理对重症急性胰腺炎（SAP）家兔的TNF-α、IL-6的影响。方法24只雄性日本大耳白兔随机分为栀子苷预处理组、SAP模型组和假手术组,SAP模型采用5%牛磺胆酸钠溶液逆行胰胆管注射方法建立。检测不同时段血清淀粉酶、血清Ca2＋、肿瘤坏死因子-α（TNF-α）、细胞白介素（IL-6）水平,光镜下观察胰腺组织的病理变化。结果家兔SAP造模后6h开始出现TNF-α、IL-6和血淀粉酶水平升高,血清Ca2＋水平降低,栀子苷预处理组各时点TNF-α、IL-6和血淀粉酶水平较对照组明显下降,血清Ca2＋水平较SAP模型组明显降低缓慢。光镜下可见SAP家兔的胰腺组织存在明显的变性、坏死等病理损伤,栀子苷预处理组胰腺病理损伤明显减轻。结论栀子苷预处理能抑制TNF-α、IL-6在胰腺组织中的活化,从而下调细胞因子的表达,减轻SAP家兔胰腺的损伤,对SAP的胰腺具有保护作用。     

益气活血复方对慢性心力衰竭大鼠TNF-α及IL-6的影响

目的探讨中药益气活血复方对慢性心力衰竭大鼠血清中TNF-α及IL-6的影响。方法选用健康雄性Wistar大白鼠,采用冠状动脉结扎术配合饥饿、游泳等方法造成慢性心力衰竭的动物模型。将造模成功的大鼠随机分为4组:模型组、中药大剂量组、中药中剂量组和西药对照组,每组8只;另设一组正常大鼠作为对照组。喂药及正常喂养8周后,用彩色超声多普勒心动图测定大鼠心功能且采用放射免疫方法测定血清中肿瘤坏死因子-α(TNF-α),白介素6(IL-6)的含量。结果大鼠模型组心功能明显降低(P<0.01);血清中TNF-α和IL-6含量显著高于对照组(P均<0.01);中药组和西药组TNF-α及IL-6含量均低于模型组(P均<0.01)。结论益气活血复方可以降低TNF-α、IL-6的水平,改善心脏功能。     

缺氧/复氧对卵巢癌SKOV3细胞增殖能力的影响

目的:探讨缺氧/复氧后卵巢浆液性囊腺癌细胞株SKOV3增殖能力的改变及其相关机制。方法:SKOV3细胞分别缺氧24h及缺氧后复氧培养不同时间。用MTT法检测细胞的增殖,流式细胞仪检测细胞周期;Western blot和RT-PCR检测缺氧诱导因子-1α(HIF-1α)的表达。用HIF-1α抑制剂雷帕霉素(Rapamycin)预处理细胞30min后,检测上述各指标的变化。结果:复氧24h细胞增殖率增加(1.38±0.60,P=0.023);复氧48h细胞增殖率恢复为常氧培养水平(0.67±0.28,P=0.48)。流式细胞仪分析显示复氧24h时S期细胞增加[(48.45±1.15)%,P=0.013],G1期细胞减少[(45.71±2.28)%,P=0.044]。常规培养的SKOV3稳定表达HIF-1α,缺氧可使HIF-1α蛋白表达增加(P=0.0045),复氧8h,HIF-1α表达迅速下降。Rapamycin可以使细胞周期停滞于G0~G1期,从而降低细胞的增殖能力。结论:缺氧/复氧可增强卵巢癌细胞株SKOV3的增殖能力,HIF-1α通路可能在其中起重要作用。     

17 alpha-hydroxylase deficiency in a genetic male and female sibling pair

The diagnosis of congenital adrenal hyperplasia due to a deficiency of the enzyme 17 alpha-hydroxylase was made in a genetic male and female sibling pair born of parents who were first cousins. The genetic male was a phenotypic female who presented with primary amenorrhea and mild hypertension. The genetic female exhibited absence of secondary sexual characteristics and severe hypertension. The plasma steroid data confirmed the diagnosis of 17 alpha-hydroxylase deficiency in both subjects: low 17 alpha-hydroxyprogesterone, elevated desoxycorticosterone, elevated corticosterone and elevated progesterone. These are the first case reports of 17 alpha-hydroxylase deficiency in a male-female sibling pair, and they add support to the hypothesis that this is an autosomal recessive disorder.     

Successful Treatment of Essential Thrombocythemia in a Pregnancy with Recombinant Interferon-α2a

Essential thrombocythemia (ET) in pregnancy is associated with adverse perinatal outcome, which is likely due to thrombosis of the uteroplacental circulation. Obstetrical management is still controversial. Different therapeutic protocols have been adopted, including the use of aspirin, plateletpheresis, and interferon. We herein report a case of ET treated with interferon-2α from 13 weeks gestation until term. Therapy was well tolerated, leading to a linear reduction of platelet and white blood cell count that rapidly returned within normal limits. A healthy, 3,020-g male infant was delivered at 40 weeks gestation. Albeit further experience is required, recombinant interferon-α_2a may play an important role in preventing complications in pregnant patients with ET.     

Threshold serum concentrations of tumour necrosis factor alpha (TNFα) as a potential marker of the presence of microangiopathy in children and adolescents with type 1 diabetes mellitus (T1DM)

The aim of this study was to estimate the threshold serum concentrations of advanced glycation end products (AGEs) and their soluble receptors (sRAGE) as well as tumour necrosis factor alpha (TNFα), vascular endothelial growth factor₁₆₅ (VEGF₁₆₅) and interleukin-12 (IL-12) in predicting the occurrence of microangiopathy in children and adolescents with type 1 diabetes mellitus (T1DM). We studied 88 children and adolescents (age range: 6–20 yrs) with T1DM and 32 control subjects (age range: 7–20 yrs). All study participants had their daily urinary albumin excretion, HbA1c and serum creatinine levels measured, and underwent an eye examination and 24-h blood pressure monitoring. Moreover, serum concentrations of AGEs, sRAGE, TNFα, VEGF₁₆₅ and IL-12 were measured. In order to calculate the threshold values of the studied parameters, the Receiver Operating Characteristic (ROC) curve analysis was used. The results of our study have shown that among all the studied parameters a discriminative ability was found for TNFα, VEGF₁₆₅, duration of the disease, serum AGEs concentrations and daily urinary albumin excretion. However, the highest value of the area under the ROC curve (AUC_ROC) in predicting the occurrence of diabetic microangiopathy was found for serum TNFα concentrations with its threshold value of 1.7 pg/ml [AUC_ROC = 0.88 (95% CI: 0.79–0.97)]. The sensitivity and specificity for this variable was at the level of 85.7% and 94.3%, respectively. In conclusion, according to our results serum TNFα concentrations over 1.7 pg/ml may point to the presence of diabetic microangiopathy in children and adolescents T1DM.     

MicroRNA-375 sensitizes tumour necrosis factor-alpha (TNF-α)-induced apoptosis in head and neck squamous cell carcinoma in vitro

We investigated the effect of microRNA-375 (miR-375) on tumour necrosis factor-alpha (TNF-α)-induced cell death in head and neck squamous cell carcinoma, and further explored the potential molecular mechanism underlying this phenomenon. Cal27 cells were transfected with miR-375 mimic and subsequently treated with or without TNF-α (10 ng/ml). An additional group of cells were treated with TNF-α alone. The resulting morphological changes were observed, and the percentage of sub-G1 cells was measured. The protein expression and cleavage of caspase 3, caspase 8, and poly(ADP ribose) polymerase (PARP) were determined through Western blotting. The results showed a significant increase in cell death in the combination group, but not in the groups treated with miR-375 mimic, TNF-α alone, or control. The data obtained from sub-G1 cells supported the notion that miR-375 increases the accumulation of sub-G1. In the combination group, the degradation of caspase 3, caspase 8, and PARP was observed and the cleavage of these enzymes was detected. The pan-caspase inhibitor, Z-VAD, inhibited the apoptosis of Cal27 cells treated with a combination of miR-375 mimic and TNF-α. In addition, the apoptosis inhibitory proteins, cFLIP-L and cIAP1, were down-regulated in a time-dependent manner. Taken together, these data suggest that miR-375 sensitizes TNF-α-induced apoptosis, and the reduction in the expression of the apoptosis inhibitory proteins cFLIP-L and cIAP2 plays an important role in this sensitization.